AB1615 EVALUATION OF THE NOCEBO EFFECT WHEN SWITCHING FROM THE ORIGINATOR MOLECULE TO A BIOSIMILAR IN A NORMANDY RETROSPECTIVE COHORT OF PATIENTS WITH INFLAMMATORY RHEUMATISM TREATED WITH ETANERCEPT OR ADALIMUMAB (BIONORIC STUDY)
Authors: O. Hagege, T. Lequerre, C. Marcelli, R. Varin, D. Alcaix, A. J. Weber, S. D. Mihailescu, E. Duhamel, O. Vittecoq
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The cost of treating the major inflammatory rheumatic diseases (rheumatoid arthritis and spondyloarthritis) has increased dramatically since the advent of biotherapies (bDMARD). However, the appearance of the first biosimilars has led to significant healthcare savings. However, the sometimes-negative perception of these treatments by patients and practitioners can lead to the appearance of a nocebo effect. <h3>Objectives</h3> To measure the prevalence of the nocebo effect after switching from an adalimumab (ADA) or etanercept (ETA) originator to one of their biosimilars. <h3>Methods</h3> 183 patients from 4 hospital centers in Normandy (Rouen and Caen University Hospitals, Le Havre and Evreux Hospitals) were included between January 2018 and July 2022 in this retrospective study, within the framework of the Article 51 biosimilars experiment. The subjects had an inflammatory rheumatism (RA or AS) in remission, treated with ADA or ETA originator biological treatment before being switched to a biosimilar. The occurrence of a nocebo effect was considered in patients who did not maintain treatment at 12 months and had a subjective side effect. A comparative analysis of the quantitative data collected was performed before and after the switch. The side effects that led to the discontinuation of the biosimilar were identified. During the switch, a questionnaire was distributed to 30 patients to describe the topics discussed during the consultation and their feelings about the biosimilar. Finally, a univariate and then multivariate analysis was performed to identify potential risk factors associated with the occurrence of a nocebo effect. <h3>Results</h3> The nocebo effect was measured in 13.1% of patients. It was also noted that 9.2% of the group study had presented a side effect objectified by the rheumatologist, and 1.6% mixed side effects. Were considered subjective side effects the sensation of rheumatic recrudescence without objective element found, as well as a certain number of complaints. There were 15.3% of patients who experienced a reactivation of their rheumatism, 8.2% an intolerance, 1.6% an infectious event, 0.5% an allergic reaction. Concerning the evolution under treatment, the comparative analysis did not show any significant difference before and after the switch for the measured parameters, except for the duration of morning stiffness duration in the AS group (p = 0.01). Univariate and multivariate analysis did not identify any risk factors associated with the occurrence of a nocebo effect. The responses to the questionnaire made it possible to observe the themes discussed during the consultation (mainly efficacy and cost). The majority of patients interviewed reported that the biosimilar was identical to the originator in terms of safety, efficacy, mode of use and pain at the injection site. <h3>Conclusion</h3> The occurrence of a nocebo effect following a switch to a biosimilar remains acceptable regarding the savings made. It appears less frequent when the switch is supervised by the practitioner, in contrast to the rare data in the literature, where the results differ when the substitution is systematic (up to 33% in some countries). The occurrence of such an effect can be explained by a bad perception of the patient. Therapeutic education as well as a shared medical decision between patient, rheumatologist and pharmacist seems to be essential in a certain population of patients which remains to be defined. <h3>References</h3> [1] Cohen S, et al. Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study. Ann Rheum Dis. 2017;76:1679-87. [2] Glintborg B, et al. To switch or not to switch: results of a nationwide guideline of mandatory switching from originator to biosimilar etanercept. One-year treatment outcomes in 2061 patients with inflammatory arthritis from the DANBIO registry. Ann Rheum Dis. 2019;78:192-200. <h3>Acknowledgements</h3> Thanks to all the Rheumatology department of Rouen University Hospital. <h3>Disclosure of Interests</h3> None Declared.